ジャーナル: Cell / 年: 2017 タイトル: Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses. 著者: Anna Z Wec / Andrew S Herbert / Charles D Murin / Elisabeth K Nyakatura / Dafna M Abelson / J Maximilian Fels / Shihua He / Rebekah M James / Marc-Antoine de La Vega / Wenjun Zhu / Russell R ...著者: Anna Z Wec / Andrew S Herbert / Charles D Murin / Elisabeth K Nyakatura / Dafna M Abelson / J Maximilian Fels / Shihua He / Rebekah M James / Marc-Antoine de La Vega / Wenjun Zhu / Russell R Bakken / Eileen Goodwin / Hannah L Turner / Rohit K Jangra / Larry Zeitlin / Xiangguo Qiu / Jonathan R Lai / Laura M Walker / Andrew B Ward / John M Dye / Kartik Chandran / Zachary A Bornholdt / 要旨: Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has ...Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GP) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GP recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.
ダウンロード / ファイル: emd_8698.map.gz / 形式: CCP4 / 大きさ: 1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Complex of recombinant Ebola virus glycoprotein and recombinant human IgG1 Fab ADI-16061 from survivor of infection.
ボクセルのサイズ
X=Y=Z: 4.1 Å
密度
表面レベル
登録者による: 0.0443 / ムービー #1: 0.0443
最小 - 最大
-0.13251694 - 0.18348941
平均 (標準偏差)
0.00082900724 (±0.015926763)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
64
64
64
Spacing
64
64
64
セル
A=B=C: 262.4 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
4.1
4.1
4.1
M x/y/z
64
64
64
origin x/y/z
0.000
0.000
0.000
length x/y/z
262.400
262.400
262.400
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
0
0
0
NX/NY/NZ
28
11
56
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
64
64
64
D min/max/mean
-0.133
0.183
0.001
-
添付データ
-
試料の構成要素
-
全体 : EBOVGPdMuc:ADI-16061
全体
名称: EBOVGPdMuc:ADI-16061
要素
複合体: EBOVGPdMuc:ADI-16061
複合体: EBOV GPdMuc
複合体: ADI-16061 Fab
-
超分子 #1: EBOVGPdMuc:ADI-16061
超分子
名称: EBOVGPdMuc:ADI-16061 / タイプ: complex / ID: 1 / 親要素: 0 詳細: Complex of recombinant Ebola virus glycoprotein and recombinant human IgG1 Fab from survivor of infection.